Angiogenesis is VEGF-independent in the aged striatum of male rats exposed to acute hypoxia.

Brain hypoxia is involved in many diseases. The activation of angiogenesis is one of the major adaptive mechanisms to counteract the adverse effects of hypoxia. In a previous work, we have shown that the adult rat striatum promotes angiogenesis in response to hypoxia via upregulation of the most important proangiogenic factor, the vascular endothelial growth factor (VEGF). However, the effects of hypoxia on angiogenesis in the aged striatum remain unknown and constitute our aim. Here we show the upregulation of hypoxia-inducible factor-1α in the striatum of aged (24-25 months old) Wistar rats exposed to acute hypoxia and analysed during a reoxygenation period ranging from 0 h to 5 days. While the mRNA expression of the proangiogenic factors VEGF, transforming growth factor-ß1 (TGF-ß1), and adrenomedullin dropped at 0 h post-hypoxia compared to normoxic control, no changes were detected at the protein level, showing an impaired response of these proangiogenic factors to hypoxia in the aged striatum. However, the striatal blood vessel network increased at 24 h of reoxygenation, suggesting that mechanisms independent from these proangiogenic factors may be involved in hypoxia-induced angiogenesis in the striatum of aged rats. A thorough understanding of the factors involved in the response to hypoxia is essential to guide the design of therapies for hypoxia-related diseases in the aged brain.

Correlations between changes in intestinal microbiota composition and performance parameters in broiler chickens.

Growing male Cobb broiler chickens were fed on diets supplemented with additives reported as able to influence intestinal microbiota composition. The diets used were a balanced commercial diet (no additive), inulin (20 g/kg), fructose caramel (FC, 20 g/kg) and the garlic derivative PTS-O (propyl propane thiosulfonate, 45 and 90 mg/kg diet). The composition of the intestinal microbiota was analysed by qPCR at different points of the intestinal tract, and a number of nutritional parameters were also determined. The relative amounts of bacteroides (bacteroides/total bacteria) in the ileal contents correlated (p < 0.05) positively with faecal NDF, ADF, hemicellulose and cellulose digestibility. The relative amounts of Escherichia-Shigella (Escherichia-Shigella/total bacteria) in the crop contents correlated (p = 0.05) negatively with weight gain of broilers. Faecal N digestibility correlated (p < 0.05) negatively with total bacteria in the ileal contents of chickens. The relative amounts of Escherichia-Shigella (Escherichia-Shigella/total bacteria) in the caecal contents correlated (p = 0.05) negatively with faecal fat digestibility of broilers. Total bacteria in ileal or caecal contents of growing chickens correlated (p < 0.05) negatively with ileal N digestibility. The results here reported suggest that positive or negative correlations can be found between performance parameters and changes in intestinal microbiota composition of growing broiler chickens.

Risk management of radioiodine treatment in differentiated thyroid cancer.

INTRODUCTION: Patient safety is paramount in providing quality healthcare and constitutes a global concern for healthcare systems. Radioiodine treatment to patients with well-differentiated thyroid cancer is not without risks. The aim of this study is to identify, evaluate and mitigate the risks associated with this procedure. MATERIALS AND METHODS: A single-centre descriptive study was conducted in which risk management was carried out by establishing a risk map using FMEA methodology. RESULTS: Based on the process map 6 sub-processes and 23 failure modes in the three phases of the treatment process were analysed. According to risk priority number (RPN), the sub-process with the highest risk was administrative management (RPN 82), followed by treatment per se and post-treatment imaging (both with RPN 70). An overall process RPN of 300 (156 pre-treatment, 74 treatment and 70 post-treatment) was obtained. Failures directly related to the patient pose a high risk. The implementation of verification systems, performing tasks earlier and providing quality medical information are the most relevant preventive measures to be implemented. CONCLUSIONS: The application of the FMEA methodology in the risk management for radioiodine treatment is a valuable tool for improving the quality and safety of this process. The risk map has been able to identify failures at different stages, assess their causes and effects, prioritise the risks identified and implement preventive and corrective measures that can be monitored, ensuring the effectiveness of the actions taken.

Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation.

Genomic instability at simple repeated sequences (SRS) is a landmark for some sporadic and hereditary cancers of the colon. We have identified several human tumour cell lines with up to 1,000-fold increases in mutation rates for endogenous microsatellite sequences, relative to normal cells or tumour cells without the mutator phenotype and show that they are very early events in tumorigenesis. Our in vivo and in vitro results show that the genomic instability persists after transformation and that microsatellite mutations accumulate as consecutive somatic slippage events of a single or a few repeated units. This mechanism may account for the repeat expansions in triplet hereditary diseases and the same defect in replication fidelity in non-polyposis colon cancer could also contribute to the non-mendelian anticipation in these diseases.

Garlic derivative propyl propane thiosulfonate is effective against broiler enteropathogens in vivo.

Two experiments were carried out to study the effects of dietary supplementation with the garlic (Allium sativum)-derived product propyl propane thiosulfonate (PTS-O) on the intestinal log(10) number of copies of enteropathogens in broiler chickens, together with their intestinal morphology and growth performance. The additive had no significant effect on feed intake at any dose assayed. In experiment 1 (1 to 21 d of age), the BW of chickens fed on 45 mg of PTS-O/kg of diet was higher (P < 0.01) than that of controls. Birds fed on diets containing 45 and 90 mg of PTS-O/kg of diet had improved (P < 0.01) feed:gain ratios compared with the controls at 21 d of age. Ileal villus height, width and surface area, mucosal thickness, and muscular layer thickness were considerably greater (P < 0.01) than control values in chickens fed 90 mg of PTS-O/kg of diet. The Clostridium perfringens log(10) number of counts was not significantly affected at any dose assayed. The inclusion of PTS-O at both concentrations (45 and 90 mg/kg of diet) resulted in lower (P < 0.01) log(10) number of copies of ileal Salmonella spp. and crop enterobacteria and Escherichia coli. The inclusion of 90 mg of PTS-O/kg of diet also resulted in lower (P < 0.01) enterobacteria and E. coli log(10) numbers of copies in the ileal and cecal contents, respectively. The number of copies of Campylobacter jejuni was not significantly affected. In experiment 2 (15 to 28 d of age), lower (P < 0.01) log(10) number of copies of Salmonella spp. and C. jejuni were determined in the ileal contents of chickens fed on diets containing 135 mg of PTS-O/kg of diet. The addition of 90 mg of PTS-O/kg of diet lowered (P < 0.01) only the number of copies of ileal Salmonella spp. This investigation confirmed previous in vitro data and showed that PTS-O lowered the intestinal numbers of enteropathogens and improved the ileal histological structure and productive parameters of broilers.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

[Fibrous dysplasia of the bone. Contribution of nuclear medicine in the diagnosis of suspicion of sarcomatous degeneration]. / Displasia fibrosa ósea. Aportación de la Medicina Nuclear al diagnóstico de sospecha de degeneración sarcomatosa.

Fibrous dysplasia (FD) is a relatively frequent benign disease of the bone in which there is a maturation disorder of the bone-forming mesenchyme where the lamellar bone marrow is replaced with abnormal fibrous tissue. Its diagnosis is often an accidental finding when X-ray studies or bone scans are performed for other reasons since it is usually asymptomatic. There may be complications such as deformities, pathological fractures and exceptionally malignant transformation. The differential diagnosis between malignancy and FD can be complicated and lead to late diagnosis when sarcomatous degeneration already exists. In this context, the positron tomography with (18)F-fluorodeoxyglucose (FDG-PET) may be useful in the monitoring of this condition. We present two cases of patients diagnosed of FD with suspicion of malignization of their bone lesions who were referred to Nuclear Medicin.

Hydroxytyrosol as a Promising Ally in the Treatment of Fibromyalgia.

Fibromyalgia (FM) is a chronic and highly disabling syndrome, which is still underdiagnosed, with controversial treatment. Although its aetiology is unknown, a number of studies have pointed to the involvement of altered mitochondrial metabolism, increased oxidative stress and inflammation. The intake of extra virgin olive oil, and particularly of one of its phenolic compounds, hydroxytyrosol (HT), has proven to be protective in terms of redox homeostatic balance and the reduction of inflammation. In this context, using a proteomic approach with nanoscale liquid chromatography coupled to tandem mass spectrometry, the present study analysed: (i) Changes in the proteome of dermal fibroblasts from a patient with FM versus a healthy control, and (ii) the effect of the treatment with a nutritional relevant dose of HT. Our results unveiled that fibroblast from FM show a differential expression in proteins involved in the turnover of extracellular matrix and oxidative metabolism that could explain the inflammatory status of these patients. Moreover, a number of these proteins results normalized by the treatment with HT. In conclusion, our results support that an HT-enriched diet could be highly beneficial in the management of FM.

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease.

Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease.

[18F-fluorodeoxyglucose positron emission tomography in the evaluation of therapy response assessment in lymphomas. Systematic literature review and meta-analysis]. / Tomografía de positrones con 18F-fluorodesoxiglucosa en la valoración de la respuesta de los linfomas al tratamiento. Revisión sistemática de la literatura y metaanálisis.

This systematic review of literature analyze the utility of positron emission tomography (PET or PET-CT) with 18F-fluorodeoxyglucose, as a diagnostic tool in the assessment of response to chemotherapy and immunotherapy in lymphomas, in terms of diagnostic accuracy in prospective publications. A literature search was conducted in major databases and through manual review from the reference lists of articles that were recovered. The methodological quality of the selected items was evaluated using the QUADAS questionnaire. 9 publications were analyzed after the filtering process. The methodological quality of the same was broadly acceptable. In patients with LH, the negative predictive value of FDG-PET after 2-3 cycles of chemotherapy, was ranged between 93.4% (95% CI, 92.6-94.3) and 100% (95% CI, 99.3-100%), and after the treatment, the negative predictive value of PET-FDG, was between 94.3% (95% CI, 92.8-95.7) and 100% (95% CI, 97.1-100). In patients with residual masses and LH, the meta-analysis of results showed a sensitivity of 100% (95% CI, 0.753-1) and a specificity of 84% (95% CI, 0.699-0.934). PET-FDG seems to be a useful tool to evaluate the response to treatment of patients with lymphoma. However, it recommended further prospective studies and that possibly conducted in hybrid PET-CT scans, to determine its usefulness.

[Usefulness of labelled red-cell scintigraphy in Blue Rubber-Bleb Nevus syndrome]. / Utilidad de la gammagrafía con hematíes marcados en el síndrome de Blue Rubber Bleb Nevus.

Blue Rubber Bleb Nevus syndrome is a rare disorder characterized by distinctive cutaneous and gastrointestinal venous malformations that usually cause episodes of occult gastrointestinal haemorrhage and iron deficiency anaemia. We describe an 8-year-old girl who had multiple cutaneous venous malformations since birth. She also suffered from several episodes of severe chronic iron deficiency anaemia and required blood transfusions. To evaluate the presence of gastrointestinal bleeding secondary to intestinal angiomatosis, we decided to perform 99mTc-labelled red blood cell scintigraphy, which confirmed cutaneous venous malformations and also showed gastrointestinal vascular lesions that suggested the diagnosis of Blue Rubber Bleb Nevus Syndrome.

Hydroxytyrosol, the Major Phenolic Compound of Olive Oil, as an Acute Therapeutic Strategy after Ischemic Stroke.

Stroke is one of the leading causes of adult disability worldwide. After ischemic stroke, damaged tissue surrounding the irreversibly damaged core of the infarct, the penumbra, is still salvageable and is therefore a target for acute therapeutic strategies. The Mediterranean diet (MD) has been shown to lower stroke risk. MD is characterized by increased intake of extra-virgin olive oil, of which hydroxytyrosol (HT) is the foremost phenolic component. This study investigates the effect of an HT-enriched diet directly after stroke on regaining motor and cognitive functioning, MRI parameters, neuroinflammation, and neurogenesis. Stroke mice on an HT diet showed increased strength in the forepaws, as well as improved short-term recognition memory probably due to improvement in functional connectivity (FC). Moreover, mice on an HT diet showed increased cerebral blood flow (CBF) and also heightened expression of brain derived neurotrophic factor (Bdnf), indicating a novel neurogenic potential of HT. This result was additionally accompanied by an enhanced transcription of the postsynaptic marker postsynaptic density protein 95 (Psd-95) and by a decreased ionized calcium-binding adapter molecule 1 (IBA-1) level indicative of lower neuroinflammation. These results suggest that an HT-enriched diet could serve as a beneficial therapeutic approach to attenuate ischemic stroke-associated damage.

Polyphenol oxidase and its relationship with oleuropein concentration in fruits and leaves of olive (Olea europaea) cv. 'Picual' trees during fruit ripening.

Oleuropein, the main phenolic compound of olive fruit, has important antioxidant properties that are responsible for some of the nutritional properties of fruits and the defence mechanism of leaves. Polyphenol oxidase (PPO) activity changes during fruit ripening in many plants. We studied the kinetics and molecular properties of PPO in fruits and leaves of olive (Olea europaea L.) cv. 'Picual' trees and the relationship between PPO and oleuropein concentration during fruit ripening. Polyphenol oxidase showed hyperbolic kinetics in fruits and leaves. Significant increases in PPO specific activity, V(max), K(m )and catalytic efficiency occurred during fruit ripening. Based on SDS-PAGE under partially denaturing conditions and in-gel staining with DL-3,4-dihydroxyphenylalanine, PPO activity was found in one major protein of 55 and 50 kDA in fruits and leaves, respectively. During the last stages of fruit maturation, a second 36 kDa protein was observed in fruits but not in leaves, indicating that this protein could serve as a marker of the final phase of fruit maturation. Under fully denaturing conditions, only one 27.7 kDa immunoreactive band was detected in fruits. Both the amount of PPO activity and the amount of PPO protein increased significantly during fruit maturation. Immunohistochemical studies indicated that PPO is located in the epidermis, parenchyma and companion vascular cells of leaves as well as in the epidermis of fruit. During fruit maturation, oleuropein concentration measured by HPLC significantly decreased in fruits and increased in leaves.

[The role of bone scintigraphy in two cases of hereditary multiple exostoses]. / Papel de la gammagrafía ósea en dos casos de exóstosis múltiple hereditaria.

We present the cases of two patients aged 18 and 40 years, with no previous personal history of interest. The only symptoms reported by the first patient in the previous year were episodes of pain and stiffness without inflammation in the right knee and third finger of the right hand. These episodes lasted two to three weeks. Our second patient presented numbness in the lower left limb over the previous year. The analytical study was normal. The patients were diagnosed with hereditary multiple exostoses, based on the clinical, radiological and scintigraphic findings. The bone scintigraphy enabled whole body images to be obtained in a single examination and may be used for the differential diagnosis of other osteoarticular conditions, as well as for the follow-up and assessment of the response to treatment.

Resurfacing arthroplasty as an alternative to the posttraumatic sequelae of fractures of the external column of the humerus in the young adult. / Artroplastia de resuperficialización como alternativa a las secuelas postraumáticas de la columna externa del húmero en el adulto joven.

Symptomatic posttraumatic arthritis of the elbow in young patients is a disorder for which there is currently no satisfactory solution. In this case report we show the evolution of a comminuted fracture of the capitellum with trochlear extension (McKee typeIV) treated initially with open reduction and internal fixation that eventually required a resurfacing hemiarthroplasty of the capitellum and reconstruction of the lateral ligament complex. After this surgical procedure, the patient had evident improvement of pain and of elbow range of motion, keeping the possibility of performing other rescue techniques open if they were to be necessary in the future.

The nitric oxide system response to hypoxia/reoxygenation in the aged cerebral cortex.

Aged individuals are more susceptible to hypoxic insults, but little is known about the response of the nitric oxide (NO) system to hypoxia in the senescent brain. We have analysed the effect of aging on the hypobaric hypoxia/reoxygenation NO synthase (NOS) expression and activity in the cerebral cortex. In aged animals, the absence of significant changes in NOx and activity indicates a weaker response of the systems involving NO production in this pathological situation. The nNOS protein levels remained invariable and similar in both age groups after hypoxia, although in aged animals the mRNA did not change and was consistently lower than in adults. Both eNOS mRNA and protein increased shortly after hypoxia. However, although eNOS protein levels were quite similar in both age groups, the increase appeared later and was less persistent in aged animals. Real-time RT-PCR revealed a similar basal inducible NOS (iNOS) mRNA expression that responded late in reoxygenation, mainly in aged rats. However, neither iNOS protein nor activity was detected in any age group. Altogether our results indicate that aging attenuates the response of the NO system to a hypoxic injury, particularly at eNOS level, the activity of which is crucial for maintaining vascular homeostasis.

[Positron emission tomography with 18F-fluorodeoxyglucose in patients with uterine sarcoma]. / Tomografía por emisión de positrones con 18F-fluordesoxiglucosa en pacientes con sarcoma uterino.

OBJECTIVE: Describe our experience with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with uterine sarcomas, under suspicion of recurrence and in tumour staging after hysterectomy as an incidental pathology finding. MATERIAL AND METHODS: A retrospective review, between april 2002 and january 2006, of FDG-PET performed in 10 patients with clinical diagnosis of uterine sarcoma was made (7 patients under recurrence suspicion and three under initial staging). Mean age was 52.2 yrs. Evolution time after initial diagnosis vary from one month to 15 yrs (median time: 14 months). Lesions were classified as 8 leiomyosarcomas and 2 carcinosarcomas. FIGO staging were establish resulting 5 patients stage I, 1 patient stage III, and 4 patients stage IV. RESULTS: 4 of 7 patients under suspicion of recurrence showed discrepancies between positron emission tomography (PET) and conventional imaging techniques (CIT) information. FDG-PET was negative in three cases of non-conclusive CT. PET was negative in one case with pulmonary metastases. The 3 staging studies were concordant both FDG-PET and CIT images. Pathological information was obtained in 5 cases, and a mean time of 14 months of clinical follow up was made. CONCLUSIONS: FDG-PET can be useful in the follow up of uterine sarcoma patients, and also when it is an incidental finding in other causes hysterectomy.

Modifications in bacterial groups and short chain fatty acid production in the gut of healthy adult rats after long-term consumption of dietary Maillard reaction products.

Bread crust (BC) is one of the major sources of Maillard reaction products (MRPs) in the Western diet. This work was designed to analyze the impact of diets containing important levels of MRPs from BC on intestinal bacterial growth and short chain fatty acids (SCFAs) production in adult rats. Additionally, the pools of compounds excreted in feces attending to their molecular weights were analyzed. Rats were fed for 88days a control diet or diets containing BC or its soluble high molecular weight (HMW), soluble low molecular weight (LMW) or insoluble fractions, respectively. Intestinal (cecum) microbiota composition was determined by qPCR analysis. Consumption of the BC diet lowered (P<0.05) Lactobacillus spp. and Bifidobacterium spp. log10 counts (8 and 14%, respectively), an effect for which soluble LMW and HMW fractions of BC seemed to be responsible. In these same animals, Escherichia/Shigella counts increased by around 45% (P<0.05), a fact which correlated with a higher production of formic acid in feces (r=0.8197, P=0.0458), and likely caused by the combined consumption of all MRPs contained in the BC. A significant 5-fold increment (P<0.05) was detected in the fecal proportion of propionic acid in the BC group, one of the products that have largely been associated with anti-inflammatory actions. Regarding the distribution of MRPs in feces, only the LMW fed group exhibited a predominance of those ranging between 90,000-1000Da, whereas the rest of the groups presented higher amounts of products above 90,000Da. It is concluded that dietary Maillard reaction products are in vivo fermented by the gut microbiota, thereby changing both the pattern of SCFAs production and the microbiota composition.

Surgical treatment of extra-articular distal-third diaphyseal fractures of the humerus using a modified posterior approach and an extra-articular plate. / Tratamiento de las fracturas diafisarias extraarticulares de húmero distal por abordaje posterior modificado y placa extraarticular.

PURPOSE: To evaluate the clinical and radiological outcomes of these fractures treated through a modified posterior approach with a distal humerus plate. MATERIAL AND METHODS: Between 2013 and 2015 we performed a retrospective study of these fractures surgically treated in our centre. INCLUSION CRITERIA: older than 18 years old, no pathological fractures, follow up 1 year at least. 23 patients underwent surgery, mean age 45 years old, with an average follow-up of 18 months. Patient characteristics, aetiology and type of fractures were recorded. The surgery was performed using Gerwin modified posterior approach with a posterolateral distal humerus plate. Clinical results were evaluated using Quick DASH, MEPS, VAS. Radiological results were also evaluated. Complications associated with treatment and radial nerve palsy incidence were recorded as well. RESULTS: Type of fracture according AO/OTA: six 12-A, seven 12-B, ten 12-C. 23 patients progressed to union. After one year: QD 6.43, VAS 0.66, MEPS 88.88. No failure of internal fixation. Two superficial infections. 15 excellent results, 5 good, and 3 fair, with no poor results. CONCLUSION: Surgical fixation of these fractures through a modified posterior approach with a posterolateral plate minimises iatrogenic nerve injury, provides better visualisation of the proximal humerus, provides stable fixation of these injuries and results in high union rates and overall excellent functional results.

Aging affects but does not eliminate the enzymatic antioxidative response to hypoxia/reoxygenation in cerebral cortex.

The effect of aging on basal and hypoxia/reoxygenation levels of both oxidative stress (protein carbonyl and TBARS) and antioxidative-enzyme activity (Cu/Zn-SOD; Mn-SOD; Catalase, CAT; Se-independent and Se-dependent glutathione peroxidase, GPX; glutathione transferase, GST and glutathione reductase, GR) has been studied in the cerebral cortex of adult and old rats. Oxidative stress markers increased with aging and show an age-dependent post-hypoxic response. Moreover, aging caused either no change (GST, GR and CAT) or an increase (Se-GPX, Cu/Zn-SOD, Mn-SOD) in the basal activity of the enzymes analysed. Only Se-independent GPX activity decreases. However, we detected an age-dependent response of SODs to the hypoxic injury. The early and sustained Cu/Zn-SOD activity rise in adult animals became late and weak in aged animals. Meanwhile, aging slowed the Mn-SOD post-hypoxic response although this activity was consistently higher in aged rats. Aging eliminated the post-hypoxic CAT response, but, perhaps offset by increased GPX activity, did not affect the GST response and slightly reduced post-hypoxic GR activity. In conclusion, aging rise basal ROS production, does not diminish or even increase the antioxidative-enzyme activity, and may slow but does not usually eliminate the enzymatic antioxidant response to the increased post-hypoxic ROS generation.